RNAi Technology

Over the last few years, clinical pharmacology has been undergoing an enormous transformation, due to incorporation of the latest advances in the field of Molecular Biology to the development of new medicaments.

Biochemical signalling plays a critical role in cellular function, controlling both normal cell growth and also appearance of different alterations involved in the development of diverse pathologies. There are a great number of pathologies which appear as a consequence of the abnormal activity of a specific protein. In these cases, the treatment of these pathologies would be based on suppressing this activity.

The technology called RNA interference (RNAi) produces specific gene silencing via small double stranded molecules of RNA. Put more simply, an individual’s genetic information is recorded in his DNA and is organized in genes. In the cell nucleus these genes transcribe genetic information contained in their DNA into messenger RNA (mRNA). This mRNA leaves the nucleus and interacts with a ribosome, which translates the mRNA sequence into its corresponding protein/enzyme. This protein translation and synthesis may be blocked by acting on the mRNA, which is what RNA interference does.

RNA interference is a gene-specific post-transcriptional silencing mechanism where small RNA molecules which are complementary to a mRNA direct its degradation, therefore avoiding its translation into proteins.

How does it works?

Further information about how RNAi works.

Gene silencing via RNA interference is induced by small double stranded RNA molecules of between 21 and 27 nucleotides called siRNA (small interfering RNA). These siRNA suffer a series of processing rounds within the cell and as a consequence their double-stranded structure is separated into a sense strand and an antisense strand. The antisense strand hybridizes specifically to the mRNA by base-pairing, and the resulting complex is recognised by cellular mechanisms and degraded. Each siRNA is highly specific for the target nucleotide sequence it degrades. This phenomenon of gene interference occurs naturally within the organism, and is involved in development and defence against virus.

However, siRNAs may also be introduced artificially into an organism so as to silence a specific gene. Any gene with a known sequence can be the target for a siRNA designed to contain the complementary sequence to said gene. As such, siRNAs constitute a highly valuable tool for the study of gene function, therapeutic target validation, for the analysis of mechanisms of action of different medicaments, or as a therapy against diseases of genetic origin.

RNAi is a potent tool which is undergoing a grand development with therapeutic ends, due mainly to two facts: all cells contain the necessary machinery to perform RNA interference and all genes are potential targets. This technology has certain advantages when compared to different types of therapies, including a rational design based on the knowledge of the therapeutic target on which one wishes to act, high specificity and reduced secondary effects. Sylentis applies this RNAi technology to find molecules with therapeutic potential against different diseases. Said technology is applied by two different methods: via small interfering RNA fragments (siRNA) and via hairpin RNA (shRNA). These molecules allow the specific silencing of messenger RNAs which translate proteins responsible for alterations or non-desired effects within the cell, therefore inhibiting their effects. Sylentis has developed proprietary SIRFINDER™ technology, which allows us to design siRNAs with pharmacological potential, based on an optimized search of the most adequate sequences, which includes the use of bioinformatic tools, reducing research times and maximising results. Various siRNA molecules developed using this technology, have proven active against different therapeutic targets.

Over the last few years, clinical pharmacology has been undergoing an enormous transformation, due to incorporation of the latest advances in the field of Molecular Biology to the development of new medicaments.

Biochemical signalling plays a critical role in cellular function, controlling both normal cell growth and also appearance of different alterations involved in the development of diverse pathologies. There are a great number of pathologies which appear as a consequence of the abnormal activity of a specific protein. In these cases, the treatment of these pathologies would be based on suppressing this activity.

A new technology called RNA interference (RNAi) has been recently discovered. RNAi produces specific gene silencing via small double stranded molecules of RNA. Put more simply, an individual’s genetic information is recorded in his DNA and is organized in genes. In the cell nucleus these genes transcribe genetic information contained in their DNA into messenger RNA (mRNA). This mRNA leaves the nucleus and interacts with a ribosome, which translates the mRNA sequence into its corresponding protein/enzyme. This protein translation and synthesis may be blocked by acting on the mRNA, which is what RNA interference does.

RNA interference is a gene-specific post-transcriptional silencing mechanism where small RNA molecules which are complementary to a mRNA direct its degradation, therefore avoiding its translation into proteins.

Gene silencing via RNA interference is induced by small double stranded RNA molecules of between 21 and 27 nucleotides called siRNA (small interfering RNA). These siRNA suffer a series of processing rounds within the cell and as a consequence their double-stranded structure is separated into a sense strand and an antisense strand. The antisense strand hybridizes specifically to the mRNA by base-pairing, and the resulting complex is recognised by cellular mechanisms and degraded. Each siRNA is highly specific for the target nucleotide sequence it degrades. This phenomenon of gene interference occurs naturally within the organism, and is involved in development and defence against virus.

However, siRNAs may also be introduced artificially into an organism so as to silence a specific gene. Any gene with a known sequence can be the target for a siRNA designed to contain the complementary sequence to said gene. As such, siRNAs constitute a highly valuable tool for the study of gene function, therapeutic target validation, for the analysis of mechanisms of action of different medicaments, or as a therapy against diseases of genetic origin.

RNAi is a potent tool which is undergoing a grand development with therapeutic ends, due mainly to two facts: all cells contain the necessary machinery to perform RNA interference and all genes are potential targets. This technology has certain advantages when compared to different types of therapies, including a rational design based on the knowledge of the therapeutic target on which one wishes to act, high specificity and reduced secondary effects. Sylentis applies this RNAi technology to find molecules with therapeutic potential against different diseases. Said technology is applied by two different methods: via small interfering RNA fragments (siRNA) and via hairpin RNA (shRNA). These molecules allow the specific silencing of messenger RNAs which translate proteins responsible for alterations or non-desired effects within the cell, therefore inhibiting their effects. Sylentis has developed proprietary SIRFINDER™ technology, which allows us to design siRNAs with pharmacological potential, based on an optimized search of the most adequate sequences, which includes the use of bioinformatic tools, reducing research times and maximising results. Various siRNA molecules developed using this technology, have proven active against different therapeutic targets.